Drug-induced exposure of Schistosoma mansoni antigens SmCD59a and SmKK7
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Drug-induced exposure of Schistosoma mansoni antigens SmCD59a and SmKK7. / Reimers, Natalie; Homann, Arne; Höschler, Beate; Langhans, Kristina; Wilson, R Alan; Pierrot, Christine; Khalife, Jamal; Grevelding, Christoph G; Chalmers, Iain W; Yazdanbakhsh, Maria; Hoffmann, Karl F; Hokke, Cornelis H; Haas, Helmut; Schramm, Gabriele.
In: PLOS NEGLECT TROP D, Vol. 9, No. 3, 03.2015, p. e0003593.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Drug-induced exposure of Schistosoma mansoni antigens SmCD59a and SmKK7
AU - Reimers, Natalie
AU - Homann, Arne
AU - Höschler, Beate
AU - Langhans, Kristina
AU - Wilson, R Alan
AU - Pierrot, Christine
AU - Khalife, Jamal
AU - Grevelding, Christoph G
AU - Chalmers, Iain W
AU - Yazdanbakhsh, Maria
AU - Hoffmann, Karl F
AU - Hokke, Cornelis H
AU - Haas, Helmut
AU - Schramm, Gabriele
PY - 2015/3
Y1 - 2015/3
N2 - BACKGROUND: Schistosomiasis is a serious health problem especially in developing countries and affects more than 243 million people. Only few anthelmintic drugs are available up to now. A major obstacle for drug treatment is the different developmental stages and the varying host compartments during worm development. Anthelmintic drugs have been tested mainly on adult schistosomes or freshly transformed cercariae. Knowledge concerning the larval stages is lacking.METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used in vitro-grown schistosomula (aged between 2 to 14 days) to investigate drug effects of the three anthelmintics praziquantel, artemether, and oxamniquine. Further, we analyzed the antibody accessibility of two exemplary schistosome antigens SmCD59a and SmKK7, before and after drug treatment. Our results demonstrated that praziquantel applied at a concentration of 1 μM inhibited development of all life stages. Application of 10 μM praziquantel led to dramatic morphological changes of all schistosomula. Artemether at 1 and 10 μM had differential effects depending on whether it was applied to 2-day as compared to 7- and 14-day schistosomula. While 2-day schistosomula were not killed but inhibited from further development, severe morphological damage was seen in 7- and 14-day schistosomula. Oxamniquine (1 and 10 μM) led to severe morphological impairment in all life stages. Analyzing the accessibility of the antigens SmCD59a and SmKK7 before drug treatment showed no antibody binding on living intact schistosomula. However, when schistosomula were treated with anthelmintics, both antigens became exposed on the larvae. Oxamniquine turned out to be most effective in promoting antibody binding to all schistosomula stages.CONCLUSION: This study has revealed marked differences in anthelmintic drug effects against larvae. Drug treatment increases surface antigen presentation and renders larvae accessible to antibody attack.
AB - BACKGROUND: Schistosomiasis is a serious health problem especially in developing countries and affects more than 243 million people. Only few anthelmintic drugs are available up to now. A major obstacle for drug treatment is the different developmental stages and the varying host compartments during worm development. Anthelmintic drugs have been tested mainly on adult schistosomes or freshly transformed cercariae. Knowledge concerning the larval stages is lacking.METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used in vitro-grown schistosomula (aged between 2 to 14 days) to investigate drug effects of the three anthelmintics praziquantel, artemether, and oxamniquine. Further, we analyzed the antibody accessibility of two exemplary schistosome antigens SmCD59a and SmKK7, before and after drug treatment. Our results demonstrated that praziquantel applied at a concentration of 1 μM inhibited development of all life stages. Application of 10 μM praziquantel led to dramatic morphological changes of all schistosomula. Artemether at 1 and 10 μM had differential effects depending on whether it was applied to 2-day as compared to 7- and 14-day schistosomula. While 2-day schistosomula were not killed but inhibited from further development, severe morphological damage was seen in 7- and 14-day schistosomula. Oxamniquine (1 and 10 μM) led to severe morphological impairment in all life stages. Analyzing the accessibility of the antigens SmCD59a and SmKK7 before drug treatment showed no antibody binding on living intact schistosomula. However, when schistosomula were treated with anthelmintics, both antigens became exposed on the larvae. Oxamniquine turned out to be most effective in promoting antibody binding to all schistosomula stages.CONCLUSION: This study has revealed marked differences in anthelmintic drug effects against larvae. Drug treatment increases surface antigen presentation and renders larvae accessible to antibody attack.
KW - Animals
KW - Anthelmintics
KW - Antigens, Helminth
KW - Artemisinins
KW - CD59 Antigens
KW - Humans
KW - Male
KW - Praziquantel
KW - Rats
KW - Rats, Inbred BN
KW - Rats, Inbred F344
KW - Schistosoma mansoni
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1371/journal.pntd.0003593
DO - 10.1371/journal.pntd.0003593
M3 - SCORING: Journal article
C2 - 25774883
VL - 9
SP - e0003593
JO - PLOS NEGLECT TROP D
JF - PLOS NEGLECT TROP D
SN - 1935-2735
IS - 3
ER -
